Glucagon-like Peptide-1 Receptor Agonists Reduce The Risk Of Ischemic Stroke

Background and Purpose: Glucagon-like peptide-1 receptor agonists (GLP1-RA) are antihyperglycemic medications which may have a pleotropic benefit in reducing the risk of stroke. However, with ischemic stroke being the most common stroke subtype in diabetic individuals, it is currently unknown if this benefit remains present when evaluating ischemic stroke in isolation. The aim of this study was to identify whether GLP1-RA medications lower the risk of ischemic stroke. Methods: A 1:1 propensity score matched analysis of a retrospective cohort of patients from the TriNetX platform was performed with the outcome of ischemic stroke, defined with ICD-10-CM codes, during 5 years of follow-up. The exposure was prescription of a GLP1-RA, after which follow-up began. Subgroup propensity matched analyses were performed on individual GLP1-RA medications. Results: 256,938 diabetic individuals prescribed a GLP1-RA were matched with an equal cohort of unexposed diabetics. Demographic and diabetic parameters were equally matched (mean age 57.4 years, 52.5% using insulin concurrently, mean hemoglobin A1c 8.3%). Composite ischemic stroke was lower in the GLP1-RA cohort (3.5%; 8,961/256,938 versus 5.8%; 14,806/256,938) with a risk ratio of 0.61 (95% 0.59-0.62), odds ratio of 0.59 (95% CI 0.58-0.61), hazard ratio of 0.71 (95% CI 0.60-0.87), without violation of the PH assumption (p=0.4). Rate of first-time incident stroke followed a similar pattern: (1.9%; 4,746/246,735 versus 3.3%; 8,044/241,891), risk ratio of 0.58 (95% CI 0.56 - 0.60), odds ratio of 0.57 (0.57 - 0.59), hazard ratio of 0.76 (0.67 - 0.86) with preservation of the PH assumption (p= 0.25). All four GLP1-RA medications lowered the event rate of ischemic stroke. Conclusions: In our study of a large cohort of adults with diabetes, the use of a GLP1-RA reduced the risk of ischemic stroke, consistent with post-hoc analyses of randomized controlled trials.